A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial

Multiple Sclerosis Clinical Trial

— MS-tolDC  

Official title:

A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02618902
• Other study ID #: CCRG15-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 30, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: May 2021
• Source: University Hospital, Antwerp
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A first-in-human clinical trial to treat patients with multiple sclerosis by vaccination with tolerogenic dendritic cells (tolDC), generated using Good Manufacturing Practice (GMP) will be conducted. In doing so, the feasibility and safety of administering myelin-derived peptide-pulsed tolDC in patients with MS will be assessed.

Description:

A phase I dose-escalating clinical trial will be conducted in a coordinated and comprehensive manner to determine safety and tolerability, and to enable selection of a suitable dose regimen for phase II trials. The primary objective of the phase I study will be to determine whether tolDC-based therapy is safe and well tolerated and to establish the dose-response, with clinical relapse rates, neurological disability (assessed using various scales) and MRI endpoints, measured over 12 months. Patients will serve as their own controls pre- and post-vaccination. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 6 weeks. First-line treatments will be stopped 6 weeks before baseline at the latest.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9
• Est. completion date: December 31, 2021
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• MS according to 2010 revised McDonald criteria (76);

• Expanded disability status scale (EDSS) of 0-6.5 inclusive;

• Disease duration of maximum 15 years and first signs or symptoms at least 6 months prior to enrolment in the study;

• Active MS (relapsing and progressive): -1 relapse in the past year and/or

• at least 1 enhancing lesion on brain MRI in the past year

• new or enlarging T2 lesion(s) in comparison with a reference scan from maximum 1 year before

• Neurologically stable with no evidence of relapse for at least 30 days prior to start of screening and throughout during the screening phase;

• Positive T cell reactivity response to a mix of 7 myelin-derived peptides;

• Able to sign informed consent;

• Ability to comply with the protocol assessments;

• Appropriate venous access.

• Use of adequate contraceptive measures

Exclusion Criteria:

• Previous use of immunosuppressive or cytostatic treatment, including mitoxantrone, alemtuzumab or bone marrow transplantation or stem cell transplantation at any time prior to enrolment;

• Treatment with fingolimod or natalizumab or dimethylfumarate or teriflunomide within the last 3 months prior to study enrolment;

• Pregnancy or planning pregnancy in the next 12 months and breast feeding;

• Drug or alcohol abuse;

• Inability to undergo MRI assessments;

• History of or actual signs of immunodeficiency or malignancies;

• Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease;

• Hepatitis B, C, HIV, Syphilis or tuberculosis

• Splenectomy;

• Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• tolerogenic dendritic cells (tolDC)
dose-escalation

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Antwerp

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MSQOL-54	The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument	6 months
Other	whole-blood lymphocyte phenotyping - immunomonitoring	Blood samples will be analysed into detail, before and after completion of the vaccination cycle	6 months
Other	cytokine profiling - immunomonitoring	Blood samples will be analysed into detail, before and after completion of the vaccination cycle	6 months
Other	pathogenic T cell responses - immunomonitoring	myelin-specific T cell reactivity will be determined before and after completion of the vaccination cycle	6 months
Primary	Safety (Occurrence and severity of adverse events will be recorded)	Occurrence and severity of adverse events will be recorded	6 months
Primary	Feasibility (Generation of GMP-grade cell product released according to QC)	Generation of GMP-grade cell product released according to QC	6 months
Secondary	Expanded disability status scale (EDSS)	The patients' disability level well be checked during every visit	6 months
Secondary	9 Hole Peg Test (9HPT)	This is a brief, standardized, quantitative test of upper extremity function	6 months
Secondary	25 Foot walk test (T25FW)	This is a quantitative mobility and leg function performance test based on a timed 25-walk.	6 months
Secondary	Symbol Digit Modalities test (SDMT)	This test quickly screens for organic cerebral dysfunction	6 months
Secondary	Number of Gd-enhancing lesions on MRI	By means of MRI Gd-enhancing lesions will be analysed	6 months
Secondary	Number of new or enlarging T2 lesions on MRI	By means of MRI new or enlarging T2 lesions will be analysed	6 months